The process of neuronal integration takes place at the cell body and initial axon segment of the neuron where synaptic input is received and processed. One important influence on the processing of information is the character of the excitable membrane in this region of the cell. We are using voltage clamp and sensitive new method for recording current from a restricted area of membrane to map the spatial distribution of different types of ion channels across the cell surface. The goal of this project is to determine how the regional specialization of function in the neuron comes about and how a heterogeneous distribution of ion channels can be maintained. The excitability of nerve cells can be modified by various peptide hormones, but the mechanism of this important effect is not well understood. We are investigating the final steps in hormonal modulation by studying peptide effects on ionic currents in neurons of the molluscs Helix and Aplysia. We are asking where on the cell the hormone acts, which currents are modified and how. Of particular interest to us are the ionic currents that are active near the resting potential since these provide the background ionic conductance upon which neuronal integration works. Using voltage clamp methods we are studying the ionic currents near the resting potential to find the mechanism of post-inhibitory rebound and to determine if the Ca-dependent current is activated in the resting cell. Membrane ionic currents are important to the regulation of cellular activity in many types of cells, and in some cases non-neuronal cells provide excellent models for studying these regulatory events. One example is the lymphocytes of the immune system. Using membrane-patch voltage clamp, the role of the cell membrane in antigen-dependent lymphocyte activation, cell differentiation and effector cell function can be studied. We are using a cloned T-cell line that provides a particularly good preparation for study of the regulation of ion channels. Another project involves study of voltage-dependent potassium channels in the nerve cell body to further define its role in repetitive firing.